Can I take mirtazapine with Lexapro (escitalopram) if I have bradycardia?

Can Mirtazapine and Lexapro Be Combined in Patients with Bradycardia?

This combination should be avoided in patients with pre-existing bradycardia due to additive cardiac risks, particularly QT prolongation and potential for further heart rate reduction. Both medications carry independent cardiac risks that become compounded when used together, and escitalopram specifically interacts with mirtazapine to increase QT prolongation risk 1.

Primary Cardiac Concerns

Escitalopram's Direct Cardiac Effects

• Escitalopram causes QT prolongation and has documented associations with bradycardia, with the FDA and EMA imposing maximum dose restrictions particularly for patients over 60 years 1.
• SSRIs as a class increase cardiac arrest risk (OR 1.21) in large registry studies, with escitalopram and citalopram carrying the highest cardiac risk among all SSRIs 1.
• A case report documented an 82-year-old patient who developed severe sinus bradycardia (93.7% of heart rate readings <60 bpm) and sinus arrest after 3 months of escitalopram therapy, which resolved upon discontinuation 2.
• Pro-arrhythmic concentrations occur in approximately 20% of patients over 65 years taking even 10 mg escitalopram due to age-dependent reduction in drug clearance 3.

Mirtazapine's Cardiac Profile

• Mirtazapine can cause bradyarrhythmias in overdose situations, with a documented case of junctional bradycardia (heart rate 34 bpm) and severe hypotension (60/30 mmHg) requiring atropine and norepinephrine after 300 mg ingestion 4.
• While mirtazapine is generally considered to have a safer cardiac profile than tricyclic antidepressants at therapeutic doses, it blocks α2-adrenergic receptors and histamine H1 receptors, which can contribute to cardiovascular effects 5.

The Critical Drug Interaction

• The American College of Cardiology specifically lists mirtazapine as a medication that interacts with escitalopram to prolong QT interval 1.
• This additive QT prolongation creates increased risk for torsades de pointes and sudden cardiac death, particularly in patients with baseline bradycardia who already have compromised cardiac conduction 1.

Clinical Decision Algorithm

Immediate Assessment Required

If this combination is already being used:

• Obtain a 12-lead ECG immediately to measure QTc interval and assess for conduction abnormalities 1.
• Check for additional contributing factors including other QT-prolonging medications (ondansetron, domperidone, antipsychotics), beta-blockers, calcium channel blockers, or digoxin 1.
• Measure electrolytes, particularly potassium and magnesium, as hypokalemia and hypomagnesemia potentiate QT prolongation 1.
• Document baseline heart rate and blood pressure, watching for symptomatic bradycardia (heart rate <60 bpm with dizziness, lightheadedness, or syncope) 6.

Safer Alternative Strategies

Switch from escitalopram to a lower-risk SSRI:

• Paroxetine has the lowest risk of QTc prolongation among SSRIs and should be preferred in high-risk cardiac patients 1.
• However, paroxetine is a potent CYP2D6 inhibitor and should not be used with metoprolol if the patient is also on beta-blockers, as it increases metoprolol levels 4-6 fold 7.
• Sertraline represents an intermediate-risk alternative with minimal CYP2D6 inhibition, making it safer with both cardiac conditions and potential beta-blocker use 1, 7.
• Mirtazapine combined with sertraline would be safer than mirtazapine with escitalopram, as sertraline has lower QT prolongation risk and mirtazapine shows minimal CYP2D6 inhibition 7, 5.

If Combination Must Continue

When no alternative exists:

• Keep escitalopram dose ≤10 mg daily and maintain serum concentrations below 100 nM through therapeutic drug monitoring 3.
• Perform baseline ECG and repeat ECG at 1 week, 1 month, and with any dose changes 1.
• Monitor heart rate and blood pressure at each visit, discontinuing immediately if heart rate drops below 50 bpm or QTc exceeds 500 msec 1.
• Avoid all other QT-prolonging medications including antiemetics (ondansetron, domperidone), antipsychotics, and certain antibiotics 1.

Critical Pitfalls to Avoid

• Never combine escitalopram with mirtazapine in patients with congenital long QT syndrome, pre-existing significant bradycardia (<50 bpm), or electrolyte abnormalities 1.
• Do not assume therapeutic doses are safe in older patients (>65 years), as age-related pharmacokinetic changes dramatically increase escitalopram levels 3.
• Avoid adding this combination to patients already taking SA or AV nodal-blocking agents (beta-blockers, diltiazem, verapamil, digoxin) without cardiology consultation 8.

Management of Acute Symptomatic Bradycardia

If bradycardia with hemodynamic compromise develops:

• Administer atropine 0.5-1 mg IV, repeated every 3-5 minutes up to 3 mg total 8, 1.
• Consider epinephrine (2-10 µg/min) or dopamine (2-10 µg/kg/min) if atropine fails 8.
• Discontinue both escitalopram and mirtazapine immediately 2.
• Transcutaneous pacing may be necessary if pharmacotherapy fails, though second-line vasopressors should be attempted first 8.

The evidence strongly supports avoiding this combination in patients with bradycardia, with safer alternatives readily available that maintain antidepressant efficacy without compounding cardiac risk 1, 7.